title: Total mortality by elevated transferrin saturation in patients with diabetes.
abstract: OBJECTIVE
  It is not known to what extent iron overload predicts prognosis in patients with diabetes after diagnosis or whether iron overload is a risk factor independent of the HFE genotype. We investigated total and cause-specific mortality according to increased transferrin saturation (≥ 50 vs. <50%), whether mortality is driven by the HFE genotype, and whether early measurement of transferrin saturation helps to predict mortality outcome.
  
  
  METHODS
  Cohort 1 included patients with late-onset type 1 diabetes (n = 716) with a cross-sectional measurement of transferrin saturation and HFE genotype. Cohort 2 included consecutively recruited patients with any diabetes (n = 6,120), transferrin saturation measurement at referral, and HFE genotype if transferrin saturation was above 50%.
  
  
  RESULTS
  In cohort 1, the hazard ratio for total mortality was 2.3 (95% CI 1.3-3.9; P = 0.002) and for cause-specific mortality by neoplasms was 5.8 (2.4-14; P = 0.00007) in patients with transferrin saturation ≥ 50 vs. <50%. Excluding genotypes C282Y/C282Y and C282Y/H63D gave similar results. The hazard ratio for total mortality was 4.0 (1.2-13; P = 0.01) and for cause-specific mortality by neoplasms was 13 (3.6-49; P = 0.0001) in patients with C282Y/C282Y versus wild type. In cohort 2, total mortality was not different in patients with transferrin saturation ≥ 50 vs. <50%. In patients with late-onset type 1 diabetes and transferrin saturation ≥ 50%, the hazard ratio for total mortality was 0.4 (0.2-0.9; P = 0.03) in cohort 2 versus cohort 1.
  
  
  CONCLUSIONS
  Increased transferrin saturation and HFE genotype C282Y/C282Y predict total mortality in patients with late-onset type 1 diabetes, and increased transferrin saturation after diagnosis is an independent risk factor. Early measurement of transferrin saturation in these patients leading to early intervention improves life expectancy.
authors.affiliation: Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark. christina@ellervik.dk
authors.forename: Christina
authors.initials: C
authors.lastname: Ellervik
authors.forename: Henrik Ullits
authors.initials: HU
authors.lastname: Andersen
authors.forename: Anne
authors.initials: A
authors.lastname: Tybjærg-Hansen
authors.forename: Merete
authors.initials: M
authors.lastname: Frandsen
authors.forename: Henrik
authors.initials: H
authors.lastname: Birgens
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.forename: Thomas
authors.initials: T
authors.lastname: Mandrup-Poulsen
mesh_terms: D000328:Adult; D000368:Aged; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000401:mortality*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014168:Transferrin / Q000235:genetics*
chemical_list: D014168:Transferrin